The prognostic value of simultaneous tumor and serum RAS/RAF mutations in localized colon cancer

Caroline Emilie Brenner Thomsen, Ane Lindegaard Appelt, Rikke Fredslund Andersen, Jan Lindebjerg, Lars Henrik Jensen, Anders Jakobsen

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Abstract

The impact of RAS/RAF mutations in localized colon cancer needs clarification. Based on analysis of tumor-specific DNA, this study aimed at elucidating the prognostic influence of mutational status in tumor and serum using an extended panel of mutations. The study retrospectively included 294 patients with curatively resected stage I-III adenocarcinoma of the colon. Mutations in tumor and serum were determined at time of surgery. Analyses were performed with droplet digital PCR technology. Hazard ratio (HR) for the association between mutational status and survival was estimated in multivariate analysis taking known prognostic factors into account. Mutational status in tumor did not on its own have significant prognostic impact (P = 0.22). Patients with a RAS mutation simultaneously in tumor and serum had a significantly worse prognosis, overall survival (OS) (HR = 2.30, 95% CI = 1.27-4.15, P = 0.0057), and disease-free survival (DFS) (HR = 2.18, 95%CI = 1.26-3.77, P = 0.0053). BRAF mutation in the serum and proficient mismatch repair (pMMR) protein in tumor also indicated significantly worse prognosis, OS (HR = 3.45, 95% CI = 1.52-7.85, P = 0.0032) and DFS (HR = 3.61, 95% CI = 1.70-7.67, P = 0.0008). In conclusion, RAS mutations in serum, and BRAF mutation in serum combined with pMMR in tumor were strong independent prognostic factors in patients with RAS/RAF mutated tumors.

Original languageEnglish
JournalCancer Medicine
Volume6
Issue number5
Pages (from-to)928-936
ISSN2045-7634
DOIs
Publication statusPublished - 2017

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Colonic Neoplasms
Mutation
Serum
Neoplasms
DNA Mismatch Repair
Disease-Free Survival
Colon
Multivariate Analysis
Polymerase Chain Reaction
DNA
Proteins

Keywords

  • Journal Article

Cite this

@article{daff7ddcce744ab1b4f418a764500e19,
title = "The prognostic value of simultaneous tumor and serum RAS/RAF mutations in localized colon cancer",
abstract = "The impact of RAS/RAF mutations in localized colon cancer needs clarification. Based on analysis of tumor-specific DNA, this study aimed at elucidating the prognostic influence of mutational status in tumor and serum using an extended panel of mutations. The study retrospectively included 294 patients with curatively resected stage I-III adenocarcinoma of the colon. Mutations in tumor and serum were determined at time of surgery. Analyses were performed with droplet digital PCR technology. Hazard ratio (HR) for the association between mutational status and survival was estimated in multivariate analysis taking known prognostic factors into account. Mutational status in tumor did not on its own have significant prognostic impact (P = 0.22). Patients with a RAS mutation simultaneously in tumor and serum had a significantly worse prognosis, overall survival (OS) (HR = 2.30, 95{\%} CI = 1.27-4.15, P = 0.0057), and disease-free survival (DFS) (HR = 2.18, 95{\%}CI = 1.26-3.77, P = 0.0053). BRAF mutation in the serum and proficient mismatch repair (pMMR) protein in tumor also indicated significantly worse prognosis, OS (HR = 3.45, 95{\%} CI = 1.52-7.85, P = 0.0032) and DFS (HR = 3.61, 95{\%} CI = 1.70-7.67, P = 0.0008). In conclusion, RAS mutations in serum, and BRAF mutation in serum combined with pMMR in tumor were strong independent prognostic factors in patients with RAS/RAF mutated tumors.",
keywords = "Journal Article",
author = "{Brenner Thomsen}, {Caroline Emilie} and Appelt, {Ane Lindegaard} and Andersen, {Rikke Fredslund} and Jan Lindebjerg and Jensen, {Lars Henrik} and Anders Jakobsen",
note = "{\circledC} 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.",
year = "2017",
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The prognostic value of simultaneous tumor and serum RAS/RAF mutations in localized colon cancer. / Brenner Thomsen, Caroline Emilie; Appelt, Ane Lindegaard; Andersen, Rikke Fredslund; Lindebjerg, Jan; Jensen, Lars Henrik; Jakobsen, Anders.

In: Cancer Medicine, Vol. 6, No. 5, 2017, p. 928-936.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - The prognostic value of simultaneous tumor and serum RAS/RAF mutations in localized colon cancer

AU - Brenner Thomsen, Caroline Emilie

AU - Appelt, Ane Lindegaard

AU - Andersen, Rikke Fredslund

AU - Lindebjerg, Jan

AU - Jensen, Lars Henrik

AU - Jakobsen, Anders

N1 - © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

PY - 2017

Y1 - 2017

N2 - The impact of RAS/RAF mutations in localized colon cancer needs clarification. Based on analysis of tumor-specific DNA, this study aimed at elucidating the prognostic influence of mutational status in tumor and serum using an extended panel of mutations. The study retrospectively included 294 patients with curatively resected stage I-III adenocarcinoma of the colon. Mutations in tumor and serum were determined at time of surgery. Analyses were performed with droplet digital PCR technology. Hazard ratio (HR) for the association between mutational status and survival was estimated in multivariate analysis taking known prognostic factors into account. Mutational status in tumor did not on its own have significant prognostic impact (P = 0.22). Patients with a RAS mutation simultaneously in tumor and serum had a significantly worse prognosis, overall survival (OS) (HR = 2.30, 95% CI = 1.27-4.15, P = 0.0057), and disease-free survival (DFS) (HR = 2.18, 95%CI = 1.26-3.77, P = 0.0053). BRAF mutation in the serum and proficient mismatch repair (pMMR) protein in tumor also indicated significantly worse prognosis, OS (HR = 3.45, 95% CI = 1.52-7.85, P = 0.0032) and DFS (HR = 3.61, 95% CI = 1.70-7.67, P = 0.0008). In conclusion, RAS mutations in serum, and BRAF mutation in serum combined with pMMR in tumor were strong independent prognostic factors in patients with RAS/RAF mutated tumors.

AB - The impact of RAS/RAF mutations in localized colon cancer needs clarification. Based on analysis of tumor-specific DNA, this study aimed at elucidating the prognostic influence of mutational status in tumor and serum using an extended panel of mutations. The study retrospectively included 294 patients with curatively resected stage I-III adenocarcinoma of the colon. Mutations in tumor and serum were determined at time of surgery. Analyses were performed with droplet digital PCR technology. Hazard ratio (HR) for the association between mutational status and survival was estimated in multivariate analysis taking known prognostic factors into account. Mutational status in tumor did not on its own have significant prognostic impact (P = 0.22). Patients with a RAS mutation simultaneously in tumor and serum had a significantly worse prognosis, overall survival (OS) (HR = 2.30, 95% CI = 1.27-4.15, P = 0.0057), and disease-free survival (DFS) (HR = 2.18, 95%CI = 1.26-3.77, P = 0.0053). BRAF mutation in the serum and proficient mismatch repair (pMMR) protein in tumor also indicated significantly worse prognosis, OS (HR = 3.45, 95% CI = 1.52-7.85, P = 0.0032) and DFS (HR = 3.61, 95% CI = 1.70-7.67, P = 0.0008). In conclusion, RAS mutations in serum, and BRAF mutation in serum combined with pMMR in tumor were strong independent prognostic factors in patients with RAS/RAF mutated tumors.

KW - Journal Article

U2 - 10.1002/cam4.1051

DO - 10.1002/cam4.1051

M3 - Journal article

C2 - 28378527

VL - 6

SP - 928

EP - 936

JO - Cancer Medicine

JF - Cancer Medicine

SN - 2045-7634

IS - 5

ER -